This application addresses broad Challenge area (04) Perform secondary analyses of existing data to answer important clinical and preventive medicine research questions, 04-HL-104. Noninvasive cardiac imaging approaches have been particularly useful to diagnose CAD and to provide individual estimates of risk that help inform management decisions. In addition to conventional imaging approaches (e.g., myocardial perfusion SPECT), newer imaging technology including coronary computed tomography angiography (CCTA), and positron emission tomography (PET) are receiving considerable attention with the goal of improving diagnosis and risk stratification of patients with suspected or known CAD. However, the economic reality of today's medical marketplace dictates that all diagnostic modalities undergo rigorous evaluation particularly with respect to their incremental clinical value, cost-effectiveness and cost-benefit. Data are necessary to define their indications, to gain clinical acceptance amongst practicing physicians, and to justify reimbursement for these modalities amongst payers. The Study of Myocardial Perfusion and Coronary Anatomy Imaging Roles in CAD (SPARC) is a prospective, open-label, multicenter, sequentially sampled, observational registry designed to compare SPECT, PET, and CCTA imaging with respect to the primary endpoints of resource utilization and improved risk re-classification over pre-imaging data in intermediate-high CAD likelihood patients with suspected and known CAD. The study included patients enrolled at 40 study sites including 39 in the US and 1 in Canada. The study has 3 pre-specified follow-up time points: 90 days, 1 year, and 2 years, with the 90-day and 1 year time-points already completed, and the 2 year follow approximately 58% completed. The strengths of this prospective registry include a well defined patient population, geographic diversity with sites distributed across all regions of the US, a balance between practice and academic sites, a multi-modality comparison, central follow up of all patients, and a rich central imaging repository of all patient study image data. SPARC is an investigator initiated study funded through unrestricted grants from four industry sponsors. Although this study was not funded to address pre- defined questions regarding cost-effectiveness, the level of detail on post-test resource consumption patterns will provide the bases for estimation of costs and insight into the potential value of testing to guide management and to examine important differences in the effectiveness of these imaging modalities in relevant clinical subgroups (including women, diabetics, and obese patients comprising a large segment of the US population). Consequently, the proposed application under this challenge grant seek to answer the following questions: (1) What is the incremental cost-effectiveness of SPECT, PET, and CCTA as well as their respective accuracy for identification of obstructive CAD, and clinical event risk re-classification?;(2) Do these diagnostic strategies perform similarly with respect to risk prediction in all patient subgroups including women, diabetics, and obese individuals?;(3) Are these diagnostic strategies equal in identifying optimal patient management by predicting therapeutic benefit (medical therapy vs. revascularization)?;(4) Are differences between these noninvasive modalities with respect to risk prediction and cost-effectiveness influenced by the quality of image interpretation? We anticipate that the results of the proposed studies will have major implications with respect to enhancing the appropriate use of cardiac imaging for identification of CAD, risk prediction of future adverse cardiac events, and guiding patient management, while seeking venues of cost efficiency;a major goal in this era of spiraling healthcare costs. 7. Project Narrative Noninvasive imaging has been identified as one of the key factors affecting health care financing, with an annual growth rate far exceeding that of catheterization, revascularization, or acute myocardial infarction. Thus, there is a need for data comparing the clinical- and cost-effectiveness of noninvasive cardiac imaging with respect to diagnosis, calibration of future risk, and guiding management in patients with known or suspected CAD. We anticipate that the results of the proposed studies will have major implications with respect to enhancing the appropriate use of cardiac imaging for identification of CAD, risk prediction of future adverse cardiac events, and guiding patient management, while seeking venues of cost efficiency;a major goal in this era of spiraling healthcare costs.